Biomaterial-related infection of joint replacements is the second most common cause of implant failure, with serious consequences. Chronically infected replacements cannot be treated without removal of the implant, as the biofilm mode of growth protects the bacteria against antibiotics. This review discusses biofilm formation on joint replacements and the important clinical phenomenon of small-colony variants (SCVs). These slow-growing phenotypic variants often remain undetected or are misdiagnosed using hospital microbiological analyses due to their unusual morphological appearance and biochemical reactions. In addition, SCVs make the infection difficult to eradicate. They often lead to recurrence since they respond poorly to standard antibiotic treatment and can sometimes survive intracellularly.